Antifungal

Antifungals work by exploiting differences between mammalian and fungal cells to kill the fungal organism with fewer adverse effects to the host. Unlike bacteria, both fungi and humans are eukaryotes. Thus, fungal and human cells are similar at the biological level. This makes it more difficult to discover drugs that target fungi without affecting human cells.

CEF3
GP(33-41)
101827-46-7
Butenafine HCl
101827-46-7
104987-12-4
Ascomycin (FK520)
104987-12-4
107534-96-3
Tebuconazole
107534-96-3
R66905
110588-57-3
114-26-1
Sendran
114-26-1
BRL44385
114778-60-8
118021-35-5
119446-68-3
Difenoconazole
119446-68-3
1198769-38-8
Posaconazole hydrate
1198769-38-8
126-07-8
Griseofulvin
126-07-8
Antifungal agent 1
1265166-14-0
130000-40-7
Thifluzamide
130000-40-7
130-26-7
Clioquinol
130-26-7

Background


Fungi are a unique group of organisms, different from all others in their behavior and cellular organization. Fungi also have an enormous range of activities – as pathogens of crop plants or humans, as decomposer organisms, as experimental “model organisms” for investigating genetics and cell biology, and as producers of many important metabolites. The uniqueness of fungi is reflected in the fact that they have the status of a kingdom, equivalent to the plant and animal kingdoms. So, fungi represent one of the three major evolutionary branches of multicellular organisms.

All true fungi have a range of features that clearly separate them from other organisms and that serve to define the fungal kingdom (Mycota). These features are outlined below:

1. All fungi are eukaryotic. In other words, they have membrane-bound nuclei containing several chromosomes, and they have a range of membrane-bound cytoplasmic organelles (mitochondria, vacuoles, etc.). Other characterisitics, shared by all eukaryotes, include: cytoplasmic streaming, DNA that contains noncoding regions termed introns, membranes that typically contain sterols, and ribosomes of the 80S type in contrast to the 70S ribosomes of bacteria.

2. Fungi typically grow as filaments, termed hyphae (singular: hypha), which extend only at their extreme tips. So, fungi exhibit apical growth in contrast to many other filamentous organisms (e.g. filamentous green algae) which grow by repeated cell divisions within a chain of cells (intercalary growth). Fungal hyphae branch repeatedly behind their tips, giving rise to a network termed a mycelium. However, some fungi grow as single-celled yeasts (e.g. Saccharomyces cerevisiae) which reproduce by budding, and some can switch between a yeast phase and a hyphal phase in response to environmental conditions. These dimorphic fungi (with two shapes) include several species that are serious pathogens of humans. They often grow as yeast-like cells for proliferation in the body fluids but convert to hyphae for invasion of the tissues.

3.Fungi are heterotrophs (chemo-organotrophs). In other words, they need preformed organic compounds as energy sources and also as carbon skeletons for cellular synthesis. The cell wall prevents fungi from engulfing food by phagocytosis, so fungi absorb simple, soluble nutrients through the wall and cell membrane. In many cases this is achieved by secreting enzymes at the hyphal tips to degrade complex polymers and then absorbing the simple, soluble nutrients released by the depolymerase (polymer-degrading) enzymes.

4. Fungi have a distinctive range of wall components, which typically including chitin and glucans (polymers of glucose with predominantly β-1,3 and β-1,6 linkages). Short lengths of cellulose (a β-1,4-linked polymer of glucose) have been detected in some fungal walls, especially in some of the primitive fungi. However, fungi differ from plants because they do not have cellulose-rich cell walls.

5. Fungi have a characteristic range of soluble carbohydrates and storage compounds, including mannitol and other sugar alcohols, trehalose (a disaccharide of glucose), and glycogen. These compounds are similar to those of some animals – notably the arthropods – but are different from those of plants.

6. Fungi typically have haploid nuclei – an important difference from almost all other eukaryotes. However, fungal hyphae often have several nuclei within each hyphal compartment, and many budding yeasts are diploid. These differences in nuclear status and nuclear arrangements have important implications for fungal genetics.

7. Fungi reproduce by both sexual and asexual means, and typically produce spores. Fungal spores vary enormously in shape, size and other properties, related to their various roles in dispersal or dormant survival.

The major activities of fungi: pathogens, symbionts, and saprotrophs

As we have already seen, all fungi require organic nutrients for their energy source and as carbon nutrients for cellular synthesis. But a broad distinction can be made according to how these nutrients are obtained: (i) by growing as a parasite (or a pathogen – a disease-causing agent) of another living organism; (ii) by growing as a symbiont in association with another organism; or (iii) by growing as a saprotroph (saprophyte) on nonliving materials.

Fungal metabolites

Metabolites can be grouped into two broad categories.

Primary metabolites: the intermediates or end products of the common metabolic pathways of all organisms (sugars, amino acids, organic acids, glycerol, etc.) and which are essential for the normal cellular functions of fungi.

Secondary metabolites: a diverse range of compounds formed by specific pathways of particular organisms; they are not essential for growth, although they can confer an advantage to the organisms that produce them (e.g. antibiotics, fungal toxins, etc.).

Reference:

Deacon, J. W. (2013). Fungal biology. John Wiley & Sons.